Medical treatment of the female reproductive system for the prevention, control, diagnosis, and cure of disease typically involves the delivery of pharmaceutically active agents to the vaginal cavity and proximal organs. Generally, agents are put in the form of gels, foams, creams, suppositories, and dissolving tablets, or other forms generally known in the art. However, these forms of delivery have not demonstrated the ability to deliver active agents to the vaginal cavity in a controlled manner, particularly for periods of three hours or longer, while providing a high level of bioadherence and a high level of stability in environments having either high or low temperatures.
The biological characteristics of the vagina and proximal areas make it difficult to treat and deliver agents to the vaginal cavity. For example, the vaginal cavity exhibits an aqueous environment, with fluids having a pH in the range of 4.5 to 5.5 and an internal temperature of approximately 98.6° F. (37° C.). The environment of the vaginal cavity is also conducive to the growth of microorganisms, such as bacteria and fungi, including yeast, and the retention of foreign particulates, such as seminal fluid resulting from intercourse, and menstrual debris. The vaginal cavity is also characterized by the ability for considerable physical deformation, such as that resulting from sexual intercourse or insertion of tampons.
Agents, such as fungicides, have typically been used to treat ailments and afflictions in the vaginal cavity. However, the pharmaceutical and chemical activity of these agents has not reached an optimal level of effectiveness. This limitation in effectiveness is due, in part or in whole, to the inadequacy of the currently available delivery systems. In fact, the currently available delivery systems have not shown the ability to release a pharmaceutically active agent in an optimally safe manner for periods of three hours or greater, without encountering problems related to bioadherence or excessive release of the active pharmaceutical ingredient. For instance, delivery systems that are available generally begin to either solubilize, disperse or liquefy almost immediately following insertion into the vaginal cavity. Thus, these delivery systems typically have minimal bioadherence to the vaginal walls.
Conventional delivery systems having a large proportion of propylene glycol in the formulation have been used to enhance the availability of the incorporated drug. The advantage being taken of both the potential solubilization of the active pharmaceutical compound in a solvent like molecule such as propylene glycol and the increased penetration potential afforded by propylene glycol through biological membranes. This extrapolation to delivery systems for mucosal membranes can be overstated, particularly when used in the vaginal cavity. The aqueous nature of the environment provides optimum conditions for systemic absorption of solubilized active pharmaceutical compounds. Inclusion of high concentrations of compounds which solubilize active pharmaceutical agents can increase the systemic absorption potential of that agent. Though in some instances this is a desired effect, in the treatment of local mucosal infections the removal of the beneficial drug from the immediate area can prolong the treatment regime, and in some cases may cause systemic absorption of active pharmaceutical compounds to reach levels that are not beneficial.
In addition there can be physical aspects of the delivery system that are compromised by the inclusion of moderate to excessive amounts of propylene glycol. For conventional emulsions, moderate to excessive amounts propylene glycol can add to the solubilization and liquification of the delivery system in the hydrophilic environment of the vaginal cavity. For more unique emulsion systems the inclusion of higher levels of propylene glycol can lead to physical instability at both ambient and elevated temperatures.
As a result, the emulsions of conventional and unique delivery systems may not provide optimal treatment in the vaginal cavity. There is an unmet need in the art for a controlled release delivery system providing optimal treatment of vaginal ailments and afflictions. Accordingly, there is an unmet need for a delivery system providing a consistent release of a pharmaceutically active agent to the vaginal cavity, specifically a system allowing pharmaceutical activity for an extended period of time, such as at least three hours, and providing high levels of bioadherence. Furthermore, there is an unmet need in the art for a delivery system that reduces the proportion of propylene glycol in the formulation.